Transcatheter Aortic Valve Replacement in Low-Surgical Risk Patients: an updated metanalysis of extended follow-up randomized controlled trials.

The long-term safety and effectiveness of transcatheter aortic valve replacement (TAVR) compared to surgical aortic valve replacement (SAVR) in low surgical risk has not been evaluated in a pooled analysis. An electronic database search was conducted for randomized controlled trials (RCTs) with a maximal 5 years clinical and echocardiographic follow-up including low surgical risk patients underwent TAVR or SAVR. We calculated Odds Ratio (OD) and 95% confidence intervals (CIs) using a random-effects model. Subgroups analysis was performed for PPI and PVLs. Three randomized controlled trials (RCTs) were included with a total of 2611 low-surgical risk patients (STS score < 4%). Compared to SAVR, TAVR group had similar rates of all-cause of mortality (OR 0.94,95%CI 0.65 to 1.37, p value 0.75) and disabling stroke (OR 0.84, 95%CI 0.52 to 1.36, p value 0.48). No significant differences were registered in the TAVR group in terms of major cardiovascular events (OR 0.96, 95%CI 0.67 to 1.38,value 0.83), myocardial infarction (OR 0.69, 95% CI 0.34 to 1.40, p value 0.31),valve thrombosis (OR 3.11, 95%CI 0.29 to 33.47, p value 0.35), endocarditis (OR 0.71,95%CI 0.35 to 1.48, p value 0.36), aortic valve reintervention (OR 0.93, 95%CI 0.52 to 1.66, p value 0.80), and rehospitalization (OR 0.80, 95%CI 0.52 to 1.02, p value 0.07) compared to SAVR. However, TAVR patients had a higher risk of paravalvular leaks (OR 8.21, 95%CI 4.18 to 16.14, p value < 0.00001), but lower rates of new-onset atrial fibrillation (OR 0.27,95%CI 0.17 to 0.30, p value <0.0001). The rates of permanent pacemaker implantation were comparable from 1 year up to a maximum of 5 years (OR 1.32, 95%CI 0.88 to 1.97, p value 0.18). Lastly, TAVR had a greater effective orifice area (0.10 cm2/m2, 95%CI 0.05 to 0.15, p value 0.0001), but similar transvalvular mean gradients (0.60, 95%CI 3.94 to 2.73, p value 0.72). In conclusion, TAVR patients had similar long-term outcomes compared to SAVR, except for an elevated risk of PVLs in the TAVR group and increased rates of atrial fibrillation in the SAVR cohort.

Takotsubo Syndrome: impact of medical therapies on prognosis. A state of art review.

Tako-Tsubo Syndrome (TTS) presents as transient ventricular dysfunction, yet its underlying pathophysiology remains enigmatic. The prognosis of patients presenting with TTS appears to be impaired as compared to the general population and is similar to patients with acute coronary syndromes. Recent investigations have predominantly focused on elucidating therapeutic strategies associated with improved outcomes, particularly among post-menopausal female patients. Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEi) may confer a survival advantage in TTS. Notably, ACEi emerges as the sole therapeutic modality demonstrating efficacy in both acute and chronic clinical courses of TTS. Despite this, the magnitude of survival benefit remains less pronounced than anticipated. This underscores the need for further research to explore additional therapeutic pathways and optimize management strategies for this unique patient cohort. Randomized clinical trials and meta-analysis are paramount in discerning the most effective therapeutic interventions aimed at enhancing survival and ameliorating outcomes in TTS. This review aims to comprehensively synthesize evidence pertaining to the prognostic implications of cardiovascular medications in TTS management.

Cardiac resynchronization therapy in inotrope-dependent heart failure: a meta-analysis.

AIMS: The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate. METHODS AND RESULTS: We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of 'inotrope dependence' or 'inability to wean'. A meta-analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope-dependent HF patients who received CRT (mean age 64.4 years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post-CRT was 7.8 days (95% CI: 3.9 to 11.7). After 1 year of follow-up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow-up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P < 0.00001). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: -41.3 to 16.7, P < 0.00001), and mean left ventricular ejection fraction increased by 4.8% (95% CI: 3.1% to 6.6%, P < 0.00001). The mean New York Heart Association (NYHA) class post-CRT was 2.7 (95% CI: 2.5 to 3.0), with a pronounced reduction of individuals in NYHA IV (risk ratio = 0.27, 95% CI: 0.18 to 0.41, P < 0.00001). On univariate analysis, there was a higher prevalence of males (85.7% vs. 40%), a history of left bundle branch block (71.4% vs. 30%), and more pronounced left ventricular end-diastolic dilation (274.3 ± 7.2 vs. 225.9 ± 6.1 mL). CONCLUSIONS: CRT appears to be a viable option for inotrope-dependent HF, with some of these patients seeming more likely to respond.

Comparison between Imaging and Physiology in Guiding Coronary Revascularization: A Meta-Analysis.

Background: Percutaneous coronary intervention (PCI) is a widely used revascularization strategy for coronary artery disease. The choice between imaging-guided and physiology-guided PCI has been a subject of debate. This meta-analysis aims to systematically compare outcomes between imaging and physiology-guided PCI and management of intermediate coronary lesions (ICLs). Methods: A comprehensive literature search was conducted across major databases for studies published up to December 2023 following PRISMA guidelines. Seven eligible studies comparing imaging-guided and physiology-guided PCI were selected for the final analysis. Relevant outcome measures included major adverse cardiovascular events (MACE), target vessel revascularization (TVR), target vessel failure (TVF), and target lesion revascularization (TLR). Subgroup analysis was performed for ICLs. Results: A total of 5701 patients were included in the meta-analysis. After a mean follow-up of 2.1 years, imaging-guided PCI was associated with lower rates of TVR compared to physiology-guided PCI (OR 0.70, 95% CI 0.52-0.95, p = 0.02); concerning MACE, TVF, and TLR, no differences were found. When the analysis was restricted to studies considering ICLs management, there were no differences between the two techniques. Meta regression analysis did not show any impact of acute coronary syndromes (ACS) presentation on MACE and TVR. Conclusions: The findings suggest that imaging-guided PCI may reduce the need for future revascularization of the target vessel compared to the functional-guided approach, and this result was not influenced by ACS presentation. These results may have important implications for clinical practice, guiding interventional cardiologists in selecting the most appropriate guidance strategy.

Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review.

BACKGROUND AND AIMS: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. METHODS: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. RESULTS: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03). CONCLUSION: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

An innovative artificial intelligence-based method to compress complex models into explainable, model-agnostic and reduced decision support systems with application to healthcare (NEAR).

BACKGROUND AND OBJECTIVE: In everyday clinical practice, medical decision is currently based on clinical guidelines which are often static and rigid, and do not account for population variability, while individualized, patient-oriented decision and/or treatment are the paradigm change necessary to enter into the era of precision medicine. Most of the limitations of a guideline-based system could be overcome through the adoption of Clinical Decision Support Systems (CDSSs) based on Artificial Intelligence (AI) algorithms. However, the black-box nature of AI algorithms has hampered a large adoption of AI-based CDSSs in clinical practice. In this study, an innovative AI-based method to compress AI-based prediction models into explainable, model-agnostic, and reduced decision support systems (NEAR) with application to healthcare is presented and validated. METHODS: NEAR is based on the Shapley Additive Explanations framework and can be applied to complex input models to obtain the contributions of each input feature to the output. Technically, the simplified NEAR models approximate contributions from input features using a custom library and merge them to determine the final output. Finally, NEAR estimates the confidence error associated with the single input feature contributing to the final score, making the result more interpretable. Here, NEAR is evaluated on a clinical real-world use case, the mortality prediction in patients who experienced Acute Coronary Syndrome (ACS), applying three different Machine Learning/Deep Learning models as implementation examples. RESULTS: NEAR, when applied to the ACS use case, exhibits performances like the ones of the AI-based model from which it is derived, as in the case of the Adaptive Boosting classifier, whose Area Under the Curve is not statistically different from the NEAR one, even the model's simplification. Moreover, NEAR comes with intrinsic explainability and modularity, as it can be tested on the developed web application platform (https://neardashboard.pythonanywhere.com/). CONCLUSIONS: An explainable and reliable CDSS tailored to single-patient analysis has been developed. The proposed AI-based system has the potential to be used alongside the clinical guidelines currently employed in the medical setting making them more personalized and dynamic and assisting doctors in taking their everyday clinical decisions.

A randomised multicentre study of angiography- versus physiologyguided percutaneous coronary intervention in patients with coronary artery disease undergoing TAVI: design and rationale of the FAITAVI trial.

The treatment of coronary artery disease (CAD) in patients with severe aortic valve stenosis (AVS) eligible for transcatheter aortic valve implantation (TAVI) is not supported by clinical evidence, and the role of physiology over anatomy as well as the timing of coronary intervention are not defined. FAITAVI (ClinicalTrials.gov: NCT03360591) is a nationwide prospective, open-label, multicentre, randomised controlled study comparing the angiography-guided versus the physiology-guided coronary revascularisation strategy in patients with combined significant CAD and severe AVS undergoing TAVI. Significant CAD will be defined as coronary stenosis ≥50%, as assessed by visual estimation in vessels ≥2.5 mm. Physiology will be tested by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). The study will be conducted at 15 sites in Italy. In the angiography arm, percutaneous coronary intervention (PCI) will be performed either before TAVI, during the TAVI procedure - before or after the valve implantation - or within 1 month±5 days of the valve implantation, left to the operator's decision. In the physiology arm, FFR and iFR will be performed before TAVI, and PCI will be indicated for FFR ≤0.80, otherwise the intervention will be deferred. In case of borderline values (0.81-0.85), FFR and iFR will be repeated after TAVI, with PCI performed when needed. With a sample size of 320 patients, the study is powered to evaluate the primary endpoint (a composite of death, myocardial infarction, stroke, major bleeding, or ischaemia-driven target vessel revascularisation). TAVI indication, strategy and medical treatment will be the same in both groups. After discharge, patients will be contacted at 1, 6, 12 and 24 months after the procedure to assess their general clinical status, and at 12 months for the occurrence of events included in the primary and secondary endpoints. FAITAVI is the first randomised clinical trial to investigate "optimal" percutaneous coronary intervention associated with TAVI in patients with severe AVS and CAD.

Cardiovascular Disease from Pathophysiology to Risk Estimation: Is Inflammation Estimated through Perivascular Attenuation on Computed Tomography the Key?

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases.

Safety and efficacy of drug-eluting stents for patients at high risk of bleedings: A network meta-analysis.

INTRODUCTION: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. METHODS: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. RESULTS: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. CONCLUSION: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis.

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study.

AIMS: Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multi-centre cohort of contemporary ACS patients. METHODS AND RESULTS: SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Secondary endpoints were defined as any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p<0.001) and thrombus (60% vs 35%, p<0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE (PSM adjusted HR 0.70, 95% CI 0.49-0.99), but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. CONCLUSION: In patients with ACS undergoing PCI and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks.

Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis.

BACKGROUND: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. METHODS: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device-related thrombus (DRT) and major bleeding. A random-effect meta-analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta-regression analyses. RESULTS: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2-VASc and HAS-BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow-up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64-2.77; p =.44), DRT (RR 1.52; 95% CI 0.90-2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67-2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64-3.12; p =.39). CONCLUSIONS: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post-procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding.

Risk Score for Prediction of Dialysis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Dialysis is a rare but serious complication after transcatheter aortic valve replacement. We analyzed the large multicenter TRITAVI (transfusion requirements in transcatheter aortic valve implantation) registry in order to develop and validate a clinical score assessing this risk. METHODS AND RESULTS: A total of 10 071 consecutive patients were enrolled in 19 European centers. Patients were randomly assigned (2:1) to a derivation and validation cohort. Two scores were developed, 1 including only preprocedural variables (TRITAVIpre) and 1 also including procedural variables (TRITAVIpost). In the 6714 patients of the derivation cohort (age 82±6 years, 48% men), preprocedural factors independently associated with dialysis and included in the TRITAVIpre score were male sex, diabetes, prior coronary artery bypass graft, anemia, nonfemoral access, and creatinine clearance <30 mL/min per m2. Additional independent predictors among procedural features were volume of contrast, need for transfusion, and major vascular complications. Both scores showed a good discrimination power for identifying risk for dialysis with C-statistic 0.78 for TRITAVIpre and C-statistic 0.88 for TRITAVIpost score. Need for dialysis increased from the lowest to the highest of 3 risk score groups (from 0.3% to 3.9% for TRITAVIpre score and from 0.1% to 6.2% for TRITAVIpost score). Analysis of the 3357 patients of the validation cohort (age 82±7 years, 48% men) confirmed the good discrimination power of both scores (C-statistic 0.80 for TRITAVIpre and 0.81 for TRITAVIpost score). Need for dialysis was associated with a significant increase in 1-year mortality (from 6.9% to 54.4%; P=0.0001). CONCLUSIONS: A simple preprocedural clinical score can help predict the risk of dialysis after transcatheter aortic valve replacement.

Impact of statin adherence and interruption within 6 months after ST-segment elevation myocardial infarction (STEMI): Results from the real-world regional registry FAST-STEMI.

BACKGROUND: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied. AIMS: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. METHODS: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. RESULTS: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p ã€ˆ0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. CONCLUSIONS: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke.

Comparison Among Ultra-Thin Coronary Stents: A Network Meta-Analysis.

Ultrathin-strut drug-eluting stents (DES) have been related to potential improvement in stent-related outcomes compared with thicker-struts DES. However, comparisons among different ultrathin devices are lacking. All randomized controlled trials comparing ultrathin (struts thickness <70 µm) and thicker-struts DESs in an all-comers population were included. Target lesion failure (TLF), as defined by included trials, at 1-year follow-up was the primary end point. Overall mortality, myocardial infarction, target lesion revascularization (TLR), and stent thrombosis were the secondary end points. Arms of included trials were compared using network meta-analysis. Nine studies encompassing 20,081 patients were included, of which 9,509 patients had an ultrathin DES: Orsiro (evaluated in 7 arms with 8,086 patients), MiStent (1 arm with 703 patients), or Supraflex (1 arm with 720 patients). At 1-year follow-up, no significant differences were noted for TLF among these ultrathin DES. In particular, Orsiro was associated with a similar risk of TLF compared with Supraflex (risk rate 1.07, 95% confidence interval 0.59 to 1.78) and showed the highest probability of performing best in terms of TLF, myocardial infarction, and TLR. Ultrathin DES are all associated with a comparable risk of TLF compared with thicker-strut DES. In terms of TLR and TLF risk, Orsiro was the one with the highest probability of best performances, either compared with other ultrathin DES or to devices with thicker struts.

The Intrinsic Cardiac Nervous System: From Pathophysiology to Therapeutic Implications.

The cardiac autonomic nervous system (CANS) plays a pivotal role in cardiac homeostasis as well as in cardiac pathology. The first level of cardiac autonomic control, the intrinsic cardiac nervous system (ICNS), is located within the epicardial fat pads and is physically organized in ganglionated plexi (GPs). The ICNS system does not only contain parasympathetic cardiac efferent neurons, as long believed, but also afferent neurons and local circuit neurons. Thanks to its high degree of connectivity, combined with neuronal plasticity and memory capacity, the ICNS allows for a beat-to-beat control of all cardiac functions and responses as well as integration with extracardiac and higher centers for longer-term cardiovascular reflexes. The present review provides a detailed overview of the current knowledge of the bidirectional connection between the ICNS and the most studied cardiac pathologies/conditions (myocardial infarction, heart failure, arrhythmias and heart transplant) and the potential therapeutic implications. Indeed, GP modulation with efferent activity inhibition, differently achieved, has been studied for atrial fibrillation and functional bradyarrhythmias, while GP modulation with efferent activity stimulation has been evaluated for myocardial infarction, heart failure and ventricular arrhythmias. Electrical therapy has the unique potential to allow for both kinds of ICNS modulation while preserving the anatomical integrity of the system.

Long-term impact of intravascular ultrasound-guidance for percutaneous coronary intervention on unprotected left main. The IMPACTUS-LM, an observational, multicentric study.

INTRODUCTION: The potential benefit on long term outcomes of Percutaneous Coronary Intervention (PCI) on Unprotected Left Main (ULM) driven by IntraVascular UltraSound (IVUS) remains to be defined. METHODS: IMPACTUS LM-PCI is an observational, multicenter study that enrolled consecutive patients with ULM disease undergoing coronary angioplasty in 13 European high-volume centers from January 2002 to December 2015. Major Adverse Cardiovascular Events (MACEs) a composite of cardiovascular (CV) death, target vessel revascularization (TVR) and myocardial infarction (MI) were the primary endpoints, while its single components along with all cause death the secondary ones. RESULTS: 627 patients with ULM disease were enrolled, 213 patients (34%) underwent IVUS-guided PCI while 414 (66%) angioguided PCI. Patients in the two cohorts had similar prevalence of risk factors except for active smoking and clinical presentation. During a median follow-up of 7.5 years, 47 (22%) patients in the IVUS group and 211 (51%) in the angio-guided group underwent the primary endpoint (HR 0.42; 95% CI [0.31-0.58] p < 0.001). After multivariate adjustment, IVUS was significantly associated with a reduced incidence of the primary endpoint (adj HR 0.39; 95% CI [0.23-0.64], p < 0.001), mainly driven by a reduction of TVR (ad HR 0.30, 95% CI [0.15-0.62], p = 0.001) and of all-cause death (adj HR 0.47, 95% CI [0.28-0.82], p = 0.008). IVUS use, age, diabetes, side branch stenosis, DES and creatinine at admission were independent predictors of MACE. CONCLUSIONS: In patients undergoing ULM PCI, the use of IVUS was associated with a reduced risk at long-term follow-up of MACE, all-cause death and subsequent revascularization.

Increased prevalence of high-risk coronary plaques in metabolic dysfunction associated stetatotic liver disease patients: A meta-analysis.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients. METHODS: PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high-risk features (namely low-attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest. RESULTS: Twenty-four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23-1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02-1.78 and OR 2.26, 95%CI 1.57-3.23 for CAC score 0-100 and >100, respectively). An increased risk of 'high-risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42-3.19). As high-risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79-4.77 and OR 2.96, 95%CI 1.22-7.20). CONCLUSIONS: Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high-risk features as detected by CTCA.

De-escalation of dual antiplatelet therapy for patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis.

OBJECTIVES: To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). DESIGN: We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed. SETTING AND PARTICIPANTS: Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT. SEARCH METHODS: A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials. INTERVENTIONS: Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1-3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3-6 months. MAIN OUTCOME MEASURES: Primary outcome: Cardiovascular mortality. SECONDARY OUTCOMES: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE). RESULTS: 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3-6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89). CONCLUSIONS: DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3-6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not.